Effects of simvastatin on vasa vasorum and aortic endothelial function in rats / 南方医科大学学报

<p><b>OBJECTIVE</b>To investigate the effect of hyperlipidemia on vasa vasorum and vascular endothelial growth factor (VEGF) and study the role of vasa vasorum in arteriosclerosis.</p><p><b>METHODS</b>Thirty SD rats were randomized into normal control, hyperlipidemic and simvastatin treatment groups (n=10). In simvastatin group, hyperlipidemia was induced by a 4-week administration of atherogenic diet followed by a 16-week treatment with simvastatin at the daily dose of 10 mg/kg, and the rats in hyperlipidemic rats received no treatment. The changes in the aorta and vasa vasorum were examined, and serum lipid concentration and VEGF and NO levels were measured.</p><p><b>RESULTS</b>Compared with the control group, the hyperlipidemic rats showed significantly thickened intima and media aorta and increased vasa vasorum density with lowered NO level, but VEGF underwent no significant changes. Simvastatin treatment significantly reduced the thickness of the intima and media aorta and increased vasa vasorum density in comparison with those in hyperlipidemic group. Simvastatin treatment also significantly increased VEGF and NO levels and a positive correlation was noted between their levels.</p><p><b>CONCLUSION</b>Hyperlipidemia can impair the vasa vasorum and aortic endothelial function. Simvastatin increases VEGF and NO and promotes neogenesis of the vasa vasorum for the benefit of the aortic function.</p>

Effect of alpha-galactosidase A deficiency on FV leiden fibrin deposition and thrombosis in mice / 中华血液学杂志

<p><b>OBJECTIVE</b>To evaluate the effect of alpha-galactosidase A (Gla) deficiency on FV Leiden (FVL) associated thrombosis in vivo.</p><p><b>METHODS</b>To generate the mice carrying mutations in Gla and FVL and analyze the tissue fibrin deposition in organs and thrombosis.</p><p><b>RESULTS</b>In the presence of FVL, Gla deficiency greatly increased tissue fibrin deposition compared with that in wild-type [Gla(-/0) FV(Q/Q) vs. Gla(+/0) FV(Q/Q) = (0.24 +/- 0.07)% vs. (0.086 +/- 0.049)%, P < 0.0001; Gla(-/-) FV(Q/Q) vs. Gla(+/+) FV(Q/Q) = (0.32 +/- 0.03)% vs. (0.06 +/- 0.005)%, P < 0.05]. With Gla deficiency, the number of thrombi on organ sections in FVL mice was significantly increased [(Gla(-/-) FV(Q/Q) and Gla(-/0) FV(Q/Q)) vs. (Gla(+/+) FV(Q/Q) and Gla(+/0) FV(Q/Q)) = 1.9 +/- 0.7 vs. 0.3 +/- 0.1, P < 0.05].</p><p><b>CONCLUSIONS</b>Gla deficiency could be an important genetic modifier for the enhanced thrombosis associated with FVL.</p>

Leptin promotes neointimal formation by stimulating vascular smooth muscle cell proliferation through leptin receptor / 中华心血管病杂志

<p><b>OBJECTIVE</b>To evaluate the role of leptin in neointimal formation and related mechanisms.</p><p><b>METHODS</b>Femoral arterial injury was induced in wild-type (Wt, n = 10), leptin-deficient (Lep(-)/-, n = 12), and leptin receptor-deficient (LepR(-)/-, n = 10) mice. Leptin treatment studies (tail vein injection of adenovirus expressing murine leptin on the RSV promoter, ad-leptin) were performed on Lep(-)/- (n = 5) and LepR(-)/- (n = 4) mice. Intimal (I) and medial (M) areas were measured and the ratio of I/M was calculated. Smooth muscle cells were detected by smooth muscle alpha-actin staining using an alpha-actin monoclonal antibody. Cellular proliferation was analyzed with BrdU Staining Kit and the number of BrdU-positive cells was counted manually. Plasma leptin level was measured by ELISA.</p><p><b>RESULTS</b>The I/M ratio of Lep(-)/- and LepR(-)/- mice was significantly lower than that in Wt separately (Lep(-)/- vs. Wt = 0.80 +/- 0.14 vs. 1.50 +/- 0.22, P < 0.01; LepR(-)/- vs. Wt = 0.55 +/- 0.20 vs. 1.50 +/- 0.22, P < 0.05). Plasma leptin level was significantly increased in Lep(-)/- and LepR(-)/- mice post leptin treatment. I/M was significantly increased in Lep(-)/- mice receiving ad-leptin compared with untreated Lep(-)/- mice (P < 0.05), while I/M was similar between LepR(-)/- mice with and without ad-leptin treatment (P > 0.05). The changes on number of positive alpha-actin and BrdU stained smooth muscle cells were consistent with the neointimal formation findings in various groups.</p><p><b>CONCLUSIONS</b>Mice lacking leptin or the leptin receptor were protected from neointimal formation following vascular injury. Leptin treatment increased neointimal formation in Lep(-)/- but not in LepR(-)/- mice, suggesting leptin receptor activation and vascular smooth muscle cell proliferation played a pivotal role on neointimal formation post-injury in this model, giving an evidence that high plasma leptin level is a risk factor for neointimal formation.</p>

Impact of fenofibrate on NO and endothelial VCAM-1 expression in hyperlipidemic rats / 南方医科大学学报

<p><b>OBJECTIVE</b>To investigate the mechanism of hyperlipidemia- and imflammation-induced functional impairment of the endothelium.</p><p><b>METHODS</b>The experiment was conducted using 3 groups of rats fed for 20 weeks with standard chow (control group), high-fat diet and high-fat diet with daily fenofibrate treatment (10 mg/kg, starting since the fifth week), respectively. After 4 and 20 weeks of feeding, respectively, serum lipid level and NO concentration were measured in the rats, and the epithelial vascular cell adhesion molecule-1 (VCAM-1) expression and cell adhesiveness to the aortic endothelium were observed.</p><p><b>RESULTS</b>Compared with the control group, the rats with hyperlipidemia induced by long-term high-fat diet feeding showed lower NO concentration and increased leukocyte accumulation on the endothelial surface, exhibiting also stronger and more extensive endothelial expression of VCAM-1. In contrast, the hyperlipidemic rats with fenofibrate treatment shoed significantly decreased VCAM-1 expression and leukocyte adhesion with recovery of the NO level.</p><p><b>CONCLUSION</b>NO deficiency and activation of inflammation are involved in vascular impairment in rats with high-fat diet-induced hyperlipidemia, and fenofibrate can effectively prevent atherosclerosis by restoring NO concentration and down-regulating VCAM-1 expression in these rats.</p>